There’s also rates of sexual side effects in excess of 70% [1] and they cause weight gain which is separately associated with depression.
In fact industry data shows a smaller gap between SSRIs and placebo than FDA data. See Figure 1. [2]
The problem with SSRIs is that serotonin receptors are all over the body including in the gonads and they play a large role in appetite regulation.
They do something but it’s not nearly what people assume.
As an obese depression-sufferer currently taking Mounjaro, these new weight loss drugs seem way more effective at treating the depression than SSRIs.
Actually losing a bit of weight with previously-unimaginable ease actually offers some genuine hope. It's not quite a miracle drug, the side-effects can be unpleasant, but when you're severely overweight they seem a small price to pay.
> Various meta-analyses have consistently reported increased IL-6 and TNF-α concentrations in depressed patients compared to healthy controls. IL-6 and TNF-α are associated with specific symptoms and behaviors that co-occur with depression. [1]
They also increase the levels of brain-derived neurotrophic factor (BDNF) and BDNF-TrkB signalling is also implicated in depression, especially major depression. [2]
Second, GLP-1 RAs yield similar changes in BDNF, TNF-alpha and interleukin levels you see in atypical antidepressants and anxiolytics like the old Soviet-era Semax [3] and Selank [4]. The former is a peptide analog of ACTH and the latter a peptide analog of tuftsin. Consequently it makes perfect sense to me that GLP-1 RAs would also have atypical antidepressant activity via the same pathway.
There's a lot more to GLP-1 RAs and depression than just making you feel better about yourself as a result of your weight loss, and I suspect we're going to hear a lot more about this in the coming years.
They also get you to the point where you feel good enough to exercise, which increases the levels of serotonin, dopamine and noradrenaline, and is also as effective as antidepressants. Unfortunately, depressed people can't bring themselves to exercise. Breaking that cycle so you can and do can only help more.
I've done a lot of digging on all this stuff over the last few years, it's really fascinating.
tl;dr: There's definitely something to your lived experience. Congratulations on getting started on your journey.
[1] https://www.nature.com/articles/s41598-025-85514-0
[2] https://pmc.ncbi.nlm.nih.gov/articles/PMC8783167/
[3] https://www.cambridge.org/core/journals/cns-spectrums/articl...
"Not much better than placebo" is burying the lede.
The real problem is that placebo performs very well in depression studies. It's a well studied phenomenon.
Effective antidepressants are marginally better than placebo in the studies because the placebo group improves so much, not because the antidepressants don't do anything.
> and are shown to be about as effective as therapy — which is actually durable.
False dichotomy. The recommendation is for people on SSRIs to also do therapy.
You don't have to choose one or the other.
> There’s also rates of sexual side effects in excess of 70% [1]
If you read further in your [1] you'll see that the rate of side effects is not "in excess of 70%" but lower, and it depends on both the medication and the dose. Switching medications and changing doses is often sufficient to ameliorate some or all of these effects.
That paper also mentions newer alternatives such as Vilazodone (SSRI plus 5-HT1A action) which are shown to have lower incidence of these side effects.
> and they cause weight gain which is separately associated with depression.
SSRIs aren't really associated with weight gain once you exclude the older ones like Paroxetine which have anticholinergic effects. A lot of studies find statistically insignificant weight loss or slight gain.
Weight gain is really a negligible decision factor in modern SSRI treatment: https://www.ccjm.org/content/ccjom/70/7/314.full.pdf
There's a lot of misinformed fear mongering in your comment.
Not outperforming a placebo means they don't actually do anything.
SSRIs are potent pharmaceutical drugs that have multiple, very strong effects.
For example, Setraline (SSRI) is one of the most effective drugs to treat premature ejaculation. It used to be prescribed for exactly this purpose (and maybe still is). If anything, this is one of the most pronounced and easily measurable effects of SSRIs.
If I took 25mg of setraline per day (extremely small dose) for a week, it would become impossible to ejaculate.
It also has a whole multitude of other effects that are more dependent on individual (age, gender, bodyweight, etc), some other effects for males are -> crushing testosterone levels, weakness.
For me personally, it turns me extremely, extremely emotional, makes me able to sleep all the time, and mentally turns you into a zombie where your lifes dreams and aspirations just disappear.
Does it help with depression? I would say no. That however doesn't mean it doesn't do anyting, because they do all sorts of things. It is a very potent and poorly understood pharmaceutical.
For example, cherry pick people who have the flu. Some people in the placebo group curing their flu in the study period shouldn't be surprising. That happens by default.
If they are comparing the effect of placebo with no treatment at all, then no, the measured effect of placebo actually can't be that. The reversion to the mean effect would appear for the no treatment at all people too.
So no one really knows, in a scientific, quantifiable sense, how people who suffer from depression evolve without treatment.
One problem with that is that SSRIs are much more accessible than therapy. In my country, they are fully covered by social security and procuring them is relatively easy, while therapy is too expensive for lots of people.
> If you read further in your [1] you'll see that the rate of side effects is not "in excess of 70%" but lower, and it depends on both the medication and the dose. Switching medications and changing doses is often sufficient to ameliorate some or all of these effects.
In my case, and according to studies I'm not the only one, the side effects can be persistent. Neither the doctors nor the medication's notice warned me of this. If I knew that when I was young, I would have made different choices.
SSRIs did help me, but it cost me a lot, and I still cry about it. Of course, there is no way to know if this is a better outcome for me than what would have happened if I managed to refuse to take them.
Or in other words: it's better than placebo.
https://pubmed.ncbi.nlm.nih.gov/7037102/
https://sci-hub.se/https://www.thelancet.com/journals/lanpsy...
>Many years ago, adequately blinded trials of tricyclic antidepressants were done, in which the placebo contained atropine, which causes dryness in the mouth like the active drugs do. These trials reported very small, clinically insignificant effects of tricyclic antidepressants compared with placebo (standardised mean difference 0·17, 95% CI 0·00–0·34).
Many double blind studies are completely broken due to side effects triggering a stronger placebo response, and this is an especially huge problem for drugs like SSRIs where a placebo gets you about 80% of the benefit of the actual drug.
Similar to the study you linked, there was a more recent study where they found that for the SSRI escitalopram (aka Lexapro), the benefits disappear when you lie and tell people that they're receiving an active placebo that mimics the side effects of an SSRI. That is, if people don't actually think they're taking an SSRI, they don't get any benefit.
https://app.dimensions.ai/details/publication/pub.1142338190
-- Monicreff et al. (2023), https://www.nature.com/articles/s41380-023-02094-z
As someone who has experience with antidepressants that goes beyond looking at numbers I can assure you that effect has been established very clearly. And it has nothing to do with placebo, only the second medication was the one that worked - it did more in three days than the first one after months on the highest dose.
These studies sound to me like the attempts to find out whether life exists on a planet by analyzing some light spectrum through a telescope. I am sure they are useful but they seem a bit blind to what's actually going on in real life.
Obviously the effect feels extremely real to you, but we wouldn't see a strong placebo effect in the numbers if people on placebos didn't genuinely feel much better.
I get that it feels like the second drug worked much better, but expectancy effects and internal narratives are extremely strong, and they're impossible to untangle at the level of an individual.
Separately, I think part of what is missing from this discussion is that we currently have no mechanism for prescribing placebos to a large portion of the population.
It might not even have anything to do with the drug itself: mental health issues tend to wax and wane on their own over time, so if someone happens to feel better right after starting a new medication, it's easy to think "oh hey this one must be working" and then that can trigger the placebo effect and turn into a positive feedback cycle.
Because just like alcohol - so do SSRIs have a very clear, pronounced psychoactive pharmaceutical effects. It's just that both effects have little to do with "depression". For example, setraline is one of the most effective drugs for PE(Premature Ejaculation), with easily measurable effect (it can be timed!).
Do depressed people feel better when they are drunk and inebriated? Maybe, probably some do? There certainly are quite a lot of people that self medicate depression with alcohol!
Do depressed people feel better when they are zombified out of their brain with SSRIs? Probably some do?
From a certain point of view, prescribing SSRIs for depression isn't all that different from prescribing alcohol for depression. Both are hepatotoxic - pretty bad for your liver.
And is just a symptom of stone-age we live in when it comes to medicine and understanding of the human body.
I think this would still be consistent with it being a placebo. (Not saying it neccesarily is, just saying we would still expect to hear these types ancedotes even if it was a placebo)
I'm trained in physics, not medicine, so I am somewhat reluctant to give my own take. I have not been on SSRIs myself but I have been the responsible one for making sure that folks take them. But I would note these points about what I see in the general discussion:
• Nobody is saying the SSRIs aren't psychoactive compounds that could maybe be helpful for at least short-term intervention. Everyone agrees on at least those two things. So, nobody is telling you that you didn't feel something helpful with that second one.
• The psychiatric practice is indeed to “shop around” not just different drugs, but different generics of the same drug. To my mind this basically proves the point: if you had had a serotonin problem, the first SSRI would have fixed it and the only question would be “can you tolerate the side effects?”. So actually what's fixing the problem is a side effect of the SSRI, it is not the main effect of boosting serotonin, but it's the other ways in which these particular drugs happen to be psychoactive.
• Your first person anecdotal experience obviously is not a disproof of a placebo effect and it cannot be—this is I think you applying a popular misconception that placebo effects “don't feel real” or “don't last” or “aren't real medicine” or whatever, but they do, and they can, and they are. In these tests there is never a control that didn't get either the medicine or the placebo, which I actually find kinda frustrating—so “placebo” also means “control group.” It's just a measure of all the things that you didn't have control over. But it's called that because they give the control group a placebo. But like I don't have control over air quality, air quality can affect sleep quality, sleep quality can affect depression, if I start my experiment during a week of bad air quality and it gets better for the rest of the experiment, that generates both a “placebo” signal and a “test” signal, even though that's not the placebo effect. If you're peeking in as a physicist you've got to remember that the body heals the vast majority of our medical problems on its own, and that psychiatric problems are even moreso because “I made a new best friend at the XYZ study, now we go for walks every day together and complain about all the things that are making us more depressed this week” can fix a psychiatric problem much more easily than, say, putting cancer in remission. So like the body heals itself, the brain heals itself, the brain also has influence over physical context (“I am going to eat some broccoli and go on a walk today”), the brain also has influence over psychosocial context (“I’m gonna go no-contact with my abusive parent,” vs “I will get stuck curled in a ball in bed saying ‘I’m useless, I’m useless’ until my physics-major housemate has to remind me to get up and drink a sip of water and swallow my medicine.”) There's just so many ways the contexts are plastic, and they are all valid medicine in that context, going no-contact with an abusive parent can absolutely be therapeutic. So, placebo means control, it doesn't mean that the healing wasn't real, it just means that the healing was out of the control of the experiment, which was only looking at this particular drug.
• Finally, because these tests are done one drug at a time, this fact that they don't beat the placebo group with the test group, comes out even more nuanced. Remember that you are not being healed by the main effect of an SSRI but one of its side-effects. The question is, is that repeatable for others with depression or did it only work for your depression because it happened to take the edge off of this or that subsystem in your brain’s feedback loops, but that subsystem isn't critical to someone else's depression? Hypothesis: the failure of SSRIs to beat placebos in these tests, means that biologically there are 20+ different “depressions” and when you are “depressed” we don't know which one you have (or maybe you have even more than one!), and each of these drugs is only able to make an impact on say five of those different depressions, and whether it is worth the side effects depends on even more concerns. Meanwhile everyone in the control group gets to cure 4 of the depressions at random, say. Does your second medicine beat the placebo? Well, not for everybody. Not even for the vast majority. But for people in your particular circumstance it does. But we don't have the ability to isolate that circumstance.
In conclusion, if you are looking at medicine as a physicist, everything is f*¢#ed and it's so much nicer to play with my quantum dots and lasers and liquid nitrogen.
Yah, serotonin is involved in a lot! I don't think that's a problem? You aren't saying it directly, but I feel like you are pointing to SSRI side effects as if they invalidate that SSRIs help depression. That's not true! People can choose if they want therapy or SSRIs or both. If your doctor has been telling you serotonin dis-regulation directly causes depression that's probably wrong - but if they tell you that SSRIs help many depressed people that's right.
Regarding helping people with depression, the numbers don't really support a strong effect especially against an active placebo that makes you feel different like atropine.
[edit] Don't misunderstand, I'm not saying that there's not a role for pharmaceuticals. Just that the data for SSRIs specifically is not nearly as compelling as the quantity of prescriptions for it would have you believe, and they probably shouldn't be front-line treatment.
What we call "depression" seems to be a complex bundle of brain mess. We group by symptom but unfortunately need to treat by cause and they are not 1:1. So SSRIs are a tool "we" have on a population level - but each individual depressed person is their own situation.
Remember that "better than a placebo" is a population-level measure. Individual people will find a SSRI helpful or hindering as they go. I think you are mixing...policy ("we shouldn't assume this works for everyone") with drug efficacy ("SSRIs don't help more than a sugar pill"). How each persons' depression works is different and up-regulating serotonin is helpful to some subset of people. We don't know why and it's not the whole population, but talking about them in this way is not helpful in my mind.
Antidepressants can be a life-changer in ways that placebo could never match, and can be necessary to even be able to go see a therapist.
The way you presented those statistics is very misleading. The 70% number for sexual side effects you quoted was actually for patients that stopped taking at last once drug for that reason. Typically patients will have to try 2-3 drugs to find something that works for them and may need to transition to a new drug when the old one is no longer effective. So it's not like those patients are facing those side effects on an ongoing basis. It's just during the initial period when they are adjusting things.
I suspect that the reason why SSRIs perform so poorly in the studies is that the amount of variation in these receptor targets is high, so some drugs actually are effectively placebos to a large fraction of people. But for other individuals they are a miracle. And if you multiply that by the number of different drugs, you can almost always find one of them that helps each patient.
This goes into your assertion about "serotonin receptors are all over the body". That's something doctors and medical researchers have known for a long time. That's why the SSRIs are tailored to the specific variants of the serotonin receptors present in the organs they want to influence. That doesn't mean they have no effect on the receptors in other organs, but that the effect is minimized to the extent possible. But I suspect that one limitation in how tightly we're able to target the right receptors has to do with individual variation - make it specific enough that it doesn't affect other organs then it doesn't work for anybody with the slightest variation in target receptor shape.
But I agree that the role serotonin plays in depression is poorly understood. But I don't agree with the implication of your post that we should stop using them. They are often helpful even in cases where therapy is insufficient, and improve outcomes in conjunction with therapy. They are too useful a tool to discard, even with their issues.
Do we need better treatments for depression? Yes, desperately. Are some people with mild, self-limiting illness taking SSRIs unnecessarily? Probably, in some places. Are many people with serious depressive illness not trying drugs that might help them? Definitely. Does denigrating the least-worst treatment for most people actually help anyone?
I don't disagree strongly with anything you've said here, but I think as someone more on the other side of this argument – that in most cases people are probably better off not taking SSRIs – that part of the problem is that people don't learn to deal with their depression anymore and as a society we don't care to help those suffering with depression beyond just telling them to take psychoactive drugs.
As a depressed person myself and someone who knows a fair few depressed people, I do believe you can learn to manage it in the vast majority of cases. I think as a society if we tried to help people understand and manage their emotions then perhaps we could help people without medicating them to be honest. It's just that medicating them is easier, as you suggest.
I don't really care what others do though. If people want to medicate then more power to them... All I can say is that in my experience it's the wrong thing to do and that the only long-term way to deal with depression is to learn to experience it without being overwhelmed or burdened by it. In this sense pushing people straight to SSRIs denies them the chance at a more lasting solution. Ideally I think SSRIs should be the last option.
There's some inconsistencies in your logic there. If SSRIs aren't effective, how is it that people "don't learn to deal with their depression" due to SSRIs?
> As a depressed person myself and someone who knows a fair few depressed people, I do believe you can learn to manage it in the vast majority of cases.
The evidence supports that. The evidence also supports that without help, a lot of people won't learn to manage it, and many will literally die because of it.
Not waste money on useless treatments? Seek out other treatments like TMS (SAINT protocol), ECT, ketamine?
I don't know why you suggest that useless treatments are better than nothing. You could also throw in prayer, naturopathy, and seeking a psychic.
Americans hate to hear this: Not all problems have solutions. Really.
Way more depression than anyone is aware is clinical depression.
Address the issues in your life, and your long-tail health.
For me, it was multiple systemic infections - took the drugs and buried it down, didn't realize until it got really bad. Luckily I was young enough to survive the mistake.
If your endocrine system is doing the wrong thing, ask why.
I don't know what you wanted to say here. Clinical depression is typically used as an explicit emphasis to either emphasise that it is professionally diagnosed (as opposed to layman observations), or to emphasise that it is depression so bad it requires hospitalization (such as people who are so depressed they literally can't get out of bed for days on end).
But you seem to be using this term to mean "depression symptoms caused by other diseases"?
It’s also called Major depressive disorder. It’s basically depression that isn’t a temporary response to something. It’s long lasting depression that doesn’t go away.
You can easily look up the diagnostic criteria online.
Thanks.
By the way, a common cause for (usually light) secondary depression that more people should know about is vitamin D deficiency, quite common for even slightly darker skinned-people living in Northern Europe.
I had severe depression during Covid, manifesting as involuntary and passive suicidal ideation. Basically a hours long whirlpool of daydreaming about dying in some way, because it was the only thing which brought comfort to what I would best describe as a sort of mental agony, but without pain. Just the constant need to escape existing. Passive meaning at no point was I actively intending to act on it, but obviously this was not something to be allowed to continue.
The depression basically severely reduced my ability to mitigate my ADHD symptoms, causing them to become very apparent, essentially being co-morbid with each other. With that context, I first did some non-stimulant preliminary alternatives like:
* Bupropion HCL. This provided partial mitigation of the depression. Basically it was manageable and not threatening to implode my ability to do basic life tasks. No effect on my ADHD.
* And Atomoxetine (Strattera) which within the week had brought back my involuntary hours long daydreams of dying, and really fucked up my dick/physical and mental sexual response, which lingered for a few months after despite quickly ending treatment. As a male, I severely underestimated how much having a healthy sexual response contributes to overall wellbeing.
After that I tried extended release Dextroamphetamine.
The very first day, I wasn’t what I would consider euphoric, but I had a distinct calm sort of sense of wellbeing that was very much in contrast to the previous several months. Basically I could actually start to feel that things could be better, rather than trying to brute force reason while suffering. I liken it to what you feel when the pain from when you stub your toe fades, and you have some minor lingering endorphins.
After that first day, I didn’t feel anything else directly connected to taking the pill after that. I’d typically forget if I already took the pills 2-3 times a week (meaning skip the dose). All I could notice after resuming after skipping a day, was being slightly more chatty, and feeling like I was slightly worse at driving. The few times I probably doubled up, I’d feel this sort of mild head pressure.
But the overall effect of Dextroamphetamine within 3 days was the complete elimination of my passive ideation. Intrusive thoughts are like flies, they land on everyone, but healthy people can brush them away. I still had to take care not to voluntarily sustain negative thoughts, but it was actually voluntary now.
I later moved to Lisdexamfetamine ER because the supply of dex at the time was severely constrained, but it was basically identical. Supposedly less addictive/abusable too, though for me either felt as addictive as a collagen supplement.
After a few months, I had the dose lowered, and several months later, I halted taking stimulants. They didn’t really do much for my ADHD symptoms, and I felt that whatever had triggered my depression had cleared up so I could manually deal with the symptoms like I always have.
So that left some mild side effects of slight head pressure, probably being a slightly worse driver, probably being a slight detriment to my sleep, and possibly increasing jaw clenching (I now have a fitted nightguard), so I had zero reason to continue.
But it’s very reassuring that if I get another severe depression episode for some reason, I now have a first response tool I can use.
I'm sure you know Bupropion doesn't affect seratonin, its a dopamine re-uptake inhibitor.
As someone who also doesn't seem to respond much to seratonin related meds, Burproprion worked somewhat but I suffer from increased insomnia as a side effect. I actually respond better to things mostly affecting GABA and NMDA rather than the 'classic' anti-depressents.
That said I was trialled on methylphenidate and all it did was make me procrastinate waaaay faster, so personally I'm avoiding any stimulants stronger than caffeine.
I also got slightly weirded out when I found out something I was taking interacted with the mu-opiod receptors even though it wasn't an opiate.
I had this experience as well; in particular it really impacted my ability to work/keep a job. The added stress in turn worsened my depression, etc.
Fortunately, I was able to take almost half a year off and focus on stabilizing/recovering without further damaging my career or economic status. Many people are not so fortunate.
My recommendations having dealt with it would be sunlight, exercise, weight loss and being evaluated for sleep apnea.
I'm sure there are many, many causes of depression, but I've seen a lot of people who are overweight, which causes apnea, which gives them no sleep, which makes them miserable so they feel like they can't do anything (and may thereby gain further weight). Meanwhile lack of oxygen may cause them night terrors because they're literally suffocating in their sleep (and the bad dreams / night terrors may literally relate to this). So they get anxiety when the drowning reflex goes off at bad times and they hyperventilate.
I've seen more good from this than drugs, which may just leave someone sleepy and non-functional all the time, but as always, YMMV and you should talk to your doctor.
2. Get into nature a few hours a week.
3. Write 14 gratitude letters.
4. Dance every day.
5. Be part of a community in which your competence is growing and you have a position of status and mentorship.
6. Tell the truth in your relationships.
7. Align your self with a solar / seasonal calendar.
8. Meaningful work in a healthy work environment
9. Get microbiome sorted out
10. Fast for a week, then reintroduce healthy non inflammatory foods. Have levels checked via blood panel.
—
If someone does all of these things and maintains it for 40+ days; they will feel much better.
Depression is the result of the compounding effects of a series of small, invisible daily choices and can be reversed by small daily choices.
I spent a decade in and out of suicidal depression, and am grateful to have followed an alt path and helped many others to do so.
You can remind people that are choosing to be depressed, when they choose not to begin doing thing things to build the momentum needed to not be depressed.
They may be angry. This is ok, since anger is a step towards feeling the full range emotion which is needed to heal. Anger can lead to greif which can lead to sadness which can lead to joy and gratitude.
Depression is about repression or supression of feeling, not feeling the "wrong things".
How long are these double-blind studies? Surely they're not years long to show that the placebo effect is maintained over a decade or something.
I can't find the source now - if someone can, please help me here - but there was a theory that SSRIs work exactly because of the sexual "side effects" (which means that it's not actually a side effect but the main effect). The idea would be that the depression is due to some kind of deeply rooted sexual frustration, which is alleviated when the sex drive vanishes.
but people who are depressed still improve when on SSRIs
There was a deluge of media a couple decades ago about Prozac and its dramatic effects.
A few years later, I read some report that the studies testing its efficacy had ambiguous conclusions.
This question is more complicated than it appears.
One of the biggest challenges with depression studies is that the placebo group always improves dramatically, too. Using your terms, "over 50%" of the placebo group would likely show improvements in their depression inventories.
This makes it very complicated to interpret the studies, because now you have to look for how much more the active treatment group improves relative to the placebo group.
This is a huge detail that gets abused a lot by anti-pharma people, who write headlines about how SSRIs are "barely better than placebo" and then ignore the actual statistics. Another common tactic is to try to reframe the thresholds in different terms like "effect size" and then pool studies together to try to show that the "effect size" is below some arbitrary threshold.
Another challenge is that placebo response has been getting stronger over the years and nobody really knows why. Some antidepressant studies have even been halted because, ironically, the placebo group improved so much that there numerically wasn't much room left for the active group to be statistically better given the sample size. This is less of a problem with very large scale studies where smaller margins can be shown to be more statistically significant, but those are expensive and rare.
There isn't really a question about whether or not they are effective for many patients in the world of empirical treatment. However, if you go digging through the internet you can find plenty of commentary trying to convince you they don't work. Sadly, I've had some close friends and family members delay SSRI treatment for years because they read too many of these studies, but when they finally gave in and did a trial it turned their life around. The drugs aren't perfect and don't work for every situation, but they do work for a lot of people.
In practice, the average person will fall more in the range of maybe 5-15 due to vague symptoms like "I don't sleep as well as I used to" triggering some of the points. The average depressed person who seeks treatment might fall in the range of 25-35.
Now imagine the placebo group goes in with an average score of 35 and improves to a score of 25 by the end of the test. The SSRI group improves to an average of 20 by the end of the test. Is this significant? Well, it depends on how many patients you have in the sample size.
That's the problem. There's only so much room in these scales for improvement, so when both groups improve a lot you need to have a larger sample size to get statistical significance. Getting a lot of patients in a study (hundreds) is very expensive, so it's only a small number of studies that can pull this off.
So the published results are over-sampling studies where the statistics happened to work and under-sampling studies where they didn't.
Is this really abusing anything? It seems like the correct conclusion to draw from this is we should be giving depressed people placebos instead of SSRIs
What this should tell you is that SSRIs are almost always worth trying, because you might be one of the lucky ones for whom they work great - even if chances are they won't. Psychiatric treatment always works on this basis anyway - try one drug for a few weeks, see how well it does, then decide to either adjust dose, or try something else. Most patients eventually find something that works for them, though a the minority that don't is also large, unfortunately.
> but when they finally gave in and did a trial it turned their life around
One might wonder: could this be, in potentially large part, the placebo effect? I suppose that a good answer to that question would be a very big deal.
There's a reason modern pharma are not spending any more money researching SSRI's further.